Protein kinase B or AKT (PKB/AKT) is a serine/threonine kinase which, in mammals, comprises three highly homologous members known as PKBα (AKT1), PKBβ (AKT2), and PKBγ (AKT3). PKB/AKT is activated in cells exposed to diverse stimuli such as hormones, growth factors, and extracellular matrix components. Constitutive PKB/AKT activation can occur due to amplification of PKB/AKT genes or as a result of mutations in components of the signaling pathway that activates PKB/AKT. Constitutive PKB/AKT signaling is believed to promote proliferation and increased cell survival and thereby contributing to cancer progression.
AKT3 is a promising target for use in identifying compounds to treat cancer. Such compounds inhibit the enzymatic activity of AKT3 and thereby disrupt the cell cycle and proliferation of cells. Structure-assisted drug design is one way to optimize the success of identifying such compounds. But use of this powerful methodology requires three-dimensional structural information (e.g., as obtained via X-ray diffraction of the target protein). Alternatively, inhibitors of AKT3 can be identified using assays which utilize soluble, non-crystalline AKT3.